Asthma

Question 1

What is asthma? Whats the epidemiology?

Answer 1

Common chronic inflammatory condition.

1. Airflow limitation, - often reversible- spont. Or trx
2. Airway hyper-responsivness to many stimuli
3. Indlammation of bronchi.

Epidemiology: 10-15% second decade of life.
New Zealand more common.

Question 2

Whats the awtiology of asthma?

Answer 2

1. Atopy
   Developed IgE Abs against common allergens, grass…
   Genetic (chromosome 5- gene IL4- for IL3, IL-4, 5,13) +env factors affect serum IgE.
   Env- chilfhood infections + tobacco smoke exposure. Evidence: growing up in clean environments– predismose to IgE response to all allergens.
   Extrinsic class
2. Increased responsiveness of the airways
   (⬇️FEV1) to stimuli such as inhaled histamine + methacholine.
   Intrinsic classification.

Question 3

Whats the Pathogenesis of asthma?

What happens in inflammation?

Answer 3

1. Narrowing of airways, due to smooth muscle contraction, thickening of airways by cellular infiltration + inflammation.
2. Secretions within airway lumen.

Inflammation:
Eosinophils, T Lyphocytes(initially T2) macrophages(APCs) ,mast cells, –> release inflamatory mediators.
When stimulated, these mediators release: IL3,4,5 + GM-CSF-> mast cells and eosinophils activation.
IL4-> maintenance of allergic T2 helpers, favouring swtching of antibody production by B lymphocytes to IgE. These attach to mast cells via high affinity receptors –> mediators
Prostaglandin D2, histamine, tryptase, leukotriene C4. = ‼️Immediate asthmatic repctn.
Eosinophil activation by IgE- eosinophilic cationic protein- toxic to airways.

Question 4

Pathogenesis- what happens in asthma remodelling?

What metaplastic change happens?

Answer 4

1.Airway smooth miscle undergoes hypertrophy + hyperplasia - larger fraction of wall being occupied by smooth muscle.
Further thickened wall by- deposition of collagens and matrix proteins below ❗️ the basement membrane.

2. Airway epithelia damaged- loss of ciliated columnar cells into lumen.
   Epithelium undergoes metaplasia- ⬆️ of mucus secreting goblet cells.

Question 5

What are some features and precipitating factors?

Answer 5

Allergen (Der1) faecal particles of house dust mite, .
Wheezing- viral infx, cold air, exercise, irritant dusts, vapours and fumes( tobacco + perfume)
Emotion, drugs esp cocaine smoked. NSAIDS, B-blockers (HTN, anxiety)
Work- occupational asthma- better in holidays. Vetenary medicine and animal handling (rat, mouse, rabbit urine, fur),
Bakery( wheat, rye) and laundry work- biological enzymes.

Rare- Aspergillus fumingatus - soil mould.

CF-
Wheezing, cough, chest tightness + SOB. !
Intermittent, worse at night + early morning provoked by above trieggers.
Cough without wheeze.

O/E- during attack- reduced chest expansion, prolonged expiratory time, bilateral expiratoty polymorphic wheeze.

Question 6

How would you investigate asthma?

Answer 6

Hx and response to bronchodialators - salbutamol. No single diagnostic test.

1.Demonstration of variable airflow limitation by PEFR measurement. 2.On wakinh, during day and before bed. 15% confirms reversibility and indicates that inhaled steroids may be beneficial.

Question 7

How would you manage asthma?

Answer 7

Avoid precipitating fx, no smokinh- remove exposure. Acoid B- blockers.
1. Mild intermittent asthma- symptomatic relief.
Inhaled SABA(short acting b 2 agonist) whenever required. Eg salbutamol, terbutaline. >3x a week / night waking
⬇️⬇️
2. Regular preventative therapy
SABA + Add Inhaled steroid (100-400mainly mg) - powerful anti-inflamatory agents - preventive- e.g beclometasone diproprionate, budesonide and fluticasone proprionate.
⬇️⬇️
3. Add -on therapy.
SABA+ ICS + Add LABA e.g. Salmeterol, formoterol, maybe increase ICS
⬇️⬇️
4. Persistent poor control
Increase ICS- 2000mg
Add: theophylline or LTRA
Leukortiene receptor antagonist e.g. Montelukast, zafirlukast.
Helpful in ppl who have sx despite high dose inhaled or oral corticosteroids. + pts w/ asthma aspirin induced.

5. Oral steroids- prednisilone 30mg 5 days.

Referral 4-5 step.

Question 8

What are leukotrienes?

Answer 8

Inflamatory mediators released by mast cells which cause bronchoconstriction and increased mucus production

Question 9

Airflow obstruction in asthma:

What happens?

Answer 9

Chronic airway inflammation
Inflammatory cell infiltrate: Neutrophils- sudden onset, fatal exacerbation, occupational asthma, smokers asthma. So many on steroids and still cant control them.

Eosinophils: when u induce sputum: pro- inflammatory- ectopic, allergen.tx w/ high steroids + bronchodilator- ✔️

Lymphocytes
Mast cell activatiom–> H2–> vasodilation
Epithelial cell injury

Due to inflammation:
1. Airway hypersensitivity, 2. Airflow limitation.

Cough: brown, yellow, green.
⭐️ thickened airway wall.

During asthma sx:

1: narrowed airway, limited flow.
2: tightened muscles donstrict airway
3. Inflamaed thickened airway wall.

Question 10

What can persistent inflammation lead to?

Answer 10

1. Changes in airway structure
2. Sub basement fibrosis–> fibrosed airways
3. Mucus hypersecretion
4. Epithelial injury
5. Smooth muscle hypertrophy
6. Angiogenesis due to SM hypertrophy.

Question 11

PC

Answer 11

Aropic kid w/ ezcema amd hay fever. + itchy.
Cough: variant asthma, occupational, exertional.

Wheeze, chest tightness, cough: nocturnal + dry.
SOB- worst late evening or early morning. - rest acumulates.